1. 1Challenge the future
Stability of polymersomes containing 111
In
using Perturbed Angular Correlation
spectroscopy
Anca Tacu
Supervisor: Peter Bode

2. 2Challenge the future
1. Introduction
2. Data Interpretation
3. Results & Discussion
4. Conclusion
5. Future Work

3. 3Challenge the future
Cancer
Tumour tissue
Increased permeability of blood vessels
Dysfunctional lymphatic drainage
Accumulation
nanocarriers

4. 4Challenge the future
Polymersomes
Radionuclide 111
In
Ionophore Tropolone
Chelator DTPA

5. 5Challenge the future
Polymersomes
Radionuclide 111
In
Ionophore Tropolone
Chelator DTPA

6. 6Challenge the future
Polymersomes
Radionuclide 111
In
Ionophore Tropolone
Chelator DTPA

7. 7Challenge the future
Loading efficiency
lpmoltC In
µ/5.0)( 0111 =
lpmoltC Cd
µ/86.1)( 0111 =
Efficiency of loading dependent on:
• age of stock solution
• type of buffer

8. 8Challenge the future
PAC
Measures correlation between the directions of emission of 2 consecutive
γ-rays
Directional probability of emission dependent on:
•orientation of the nuclear spin axis
•surrounding electrical field

9. 9Challenge the future
Stop,θ
Clock,t
1γ
2γ
θ
Start
Differentiate between different surrounding media of the radionuclide studied
PAC

10. 10Challenge the future
PAC
180 90
22
22 22 180 90
1
2
N N
G
A Q N N
−
= ×
× + ×
180 90
22
22 22 180 90
1
2
N N
G
A Q N N
−
= ×
× + ×
22 0.5G =
Highly perturbed 0 ≤ G22 ≤ 1 No perturbation

11. 11Challenge the future
PAC
Parameters:
• Relaxation time
• The skn(η) coefficients
• The precession frequencies: ωkn(η)
),cos()(
3
0
tsetG kn
n
kn
t
kk
k
ωλ
∑=
−
=

12. 12Challenge the future
Data interpretation
ERRONEOUS!
Standard
deviation
ValueParameter

13. 13Challenge the future
Results & Discussion
3 sets of measurements:
• 111
InCl3 crystalized and in solution at pH 2
• 111
In-DTPA and 111
In-Tropolone complexes
• 111
In loaded polymersomes

14. 14Challenge the future
Results & Discussion
Specifications
sample
Activity
sample
Time since
Calibration
Experimental Reference
Crystalized InCl3 300 kBq 10 d -0.15 0.14
-0.02
Liquid 111
InCl3 300 kBq 11 d 1.48 0.98
Liquid 111
InCl3
(liquid nitrogen)
0.08
22G
180 90
22
22 22 180 90
1
2
N N
G
A Q N N
−
= ×
× + ×
0 ≤ G22 ≤ 1
A22 = -0.0870
Q22 = 0.8066
N180-N90<0
22G

15. 15Challenge the future
Results & Discussion
Specifications sample Activity
sample
Time since
calibration
111
In-DTPA in HEPES 130 kBq 17 d 0.31
111
In-DTPA in HEPES (liquid nitrogen) -0.57
111
In-DTPA in PBS 0.57
111
In-DTPA in PBS (liquid nitrogen) -1.93
111
In-Tropolone in HEPES 420 kBq 15 d 0.04
111
In-Tropolone in PBS 0.23
111
In-Tropolone in PBS (liquid nitrogen) -1.23
22G
Issue with the detector
OR
Correlation times of molecules too small
to be detected by the PAC

16. 16Challenge the future
Stability vs. Instability
180 90
22
22 22 180 90
1
2
N N
G
A Q N N
−
= ×
× + ×
A22 = -0.0870
Q22 = 0.8066
N180-N90<0
Assumption 180o
detector stable: N180=90 000
Case 1:
N90=60 000N90=100 000
Case 2:
22 0.67G = 22 2.03G = −

17. 17Challenge the future
Results & Discussion
Specifications sample Activity
sample
Time since
calibration
200 nm polymersomes in PBS 1st
day 170 kBq 1 d 0.39
2nd
day 130 kBq 2 d 0.26
200 nm polymersomes in
HEPES
1st
day 140 kBq 9 d 0.04
2nd
day 110 kBq 10 d 0.17
400 nm polymersomes in
HEPES
2nd
day 140 kBq 10 d 0.12
800 nm polymersomes in
HEPES
2nd
day 170 kBq 10 d -0.05
22G
Size of polymersome seems not to have any influence
Perturbation in HEPES polymersome seems to be higher than in PBS ones
Does the age of stock solution matter?

18. 18Challenge the future
Conclusion
• PAC has potential
• The system seems to have technical problems
• Winfit was not a reliable software
• No final conclusions could be drawn- more measurements
should be made

19. 19Challenge the future
Future work
1. Investigate:
• the influence of In3+
• the effect of Cd2+
• life-time of polymersomes upon systemic administration
(in vivo & in vitro)
1. Was it just a problem with the detectors?
2. Purchase/ Implement a program for the data fitting

20. 20Challenge the future
Thank you